Two-point Interaction Research Articles

Intermolecular Enantioselective Amination Reactions Mediated by Visible Light and a Chiral Iron Porphyrin Complex.

In the presence of 1 mol % of a chiral iron porphyrin catalyst, various 3-arylmethyl-substituted 2-quinolones and 2-pyridones underwent an enantioselective amination reaction (20 examples; 93-99 % ee). The substrates were used as the limiting reagents, and fluorinated aryl azides (1.5 equivalents) served as nitrene precursors. The reaction is triggered by visible light which allows a facile dediazotation at ambient temperature. The selectivity of the reaction is governed by a two-point hydrogen bond interaction between the ligand of the iron catalyst and the substrate. Hydrogen bonding directs the amination to a specific hydrogen atom within the substrate that is displaced by the nitrogen substituent either in a concerted fashion or by a rebound mechanism.

The importance of the local structure of fractal aggregates

The pair correlation function, g(r), is a fundamental descriptor of the inner structure of fractal aggregates of monomers. It provides a natural tool for studying physical properties involving two-point interaction (e.g. optics of aggregates). Several domains of distances between pairs of monomers have been identified. The fractal domain (in which g(r) is a power-law) is generally dominant for large aggregates. We show here that the local behavior of g(r)—involving monomers tangent to a given monomer—is necessary for most of the quantitative applications, even if that local domain is not directly related to fractal morphology. We derive a simple generic pair correlation function for fractal aggregates, depending on three structural parameters only: the fractal dimension, df ; the prefactor, kf ; the local mean coordination number, Zˉ . Unlike the fractal dimension, the prefactor and the mean coordination number are not universal since they depend on many parameters of the generation process. We discuss the impact of the definite shape of g(r) on the aggregate structure factor profile (a measurable quantity through small-angle x-ray scattering). Improvement from the new g(r) shape is also illustrated deriving an analytical expression of the geometric cross section, G, of aggregates for fractal dimension <2 . Accuracy is checked by comparing with numerical data from aggregates of fractal dimension df=1.9 . On the up-to-date analytical expression of G, the contributions of the short- and long-range behaviours of g(r) are well separated, and it is clear that the local behavior of the pair correlation function is required to obtain accurate values of the geometric cross section. Thus, in addition to the fractal structure of aggregates, the local structure of aggregates (to which the prefactor kf and the g(r) divergence at short distances are related) also appears important to accurately describe their physical features.

Photoinduced cross-coupling of aryl halides enabled by n-tetrabutylphosphonium phthalate

Phthalate acts as an electron shuttle bridge to realize aryl cross-coupling reactions by two-point non-covalent interaction.

The NFkB activation domain is 14-amino-acid-long variant of the 9aaTAD.

The nine-amino-acid transactivation domains (9aaTAD) was identified in numerous transcription factors including Gal4, p53, E2A, MLL, c-Myc, N-Myc, and also in SP, KLF, and SOX families. Most of the 9aaTAD domains interact with the KIX domain of transcription mediators MED15 and CBP to activate transcription. The NFkB activation domain occupied the same position on the KIX domain as the 9aaTADs of MLL, E2A, and p53. Binding of the KIX domain is established by the two-point interaction involving 9aaTAD positions p3-4 and p6-7. The NFkB primary binding region (positions p3-4) is almost identical with MLL and E2A, but secondary NFkB binding region differs by the position and engages the distal NFkB region p10-11. Thus, the NFkB activation domain is five amino acids longer than the other 9aaTADs. The NFkB activation domain includes an additional region, which we called the Omichinski Insert extending activation domain length to 14 amino acids. By deletion, we demonstrated that Omichinski Insert is an entirely non-essential part of NFkB activation domain. In summary, we recognized the NFkB activation domain as prolonged 9aaTAD conserved in evolution from humans to amphibians.

THE INSIGHT OF IN SILICO AND IN VITRO EVALUATION OF OYSTER MUSHROOM (PLEUROTUS OSTREATUS) AGAINST COLORECTAL CANCER TARGETING TIMP-1

Targeted therapy treatment in Colorectal Cancer (CRC) works specifically on a protein or target cell in cancer. It plays a role in the survival of cancer cells. Targeted therapy involves several monoclonal antibodies, one of which is cetuximab which targets the Epidermal Growth Factor Receptor (EGFR). However, there are cases of cetuximab resistance caused by activities of the Tissue Inhibitor of Metalloproteinase-1 (TIMP-1). TIMP-1 can activate the downstream EGFR signaling pathway, thereby that TIMP-1 activities need to be inhibited. Polysaccharide compounds in Pleurotus ostreatus have potential as an immunomodulator and anticancer. This study aimed to determine the potential interaction, types of bonds, the binding energy between the polysaccharide compounds Pleurotus ostreatus and TIMP-1, and survival assay of human adenocarcinoma colorectal (HT-29) cells. This research method compounds selection, data mining, compounds and proteins preparation, docking and visualization of docking results, and cell viability assay. To the study results, TIMP-1 interacted with α-glucan, β-glucan, and galactomannan, which were mediated by hydrophobic and hydrogen bonds. We found new two-point interaction of TIMP-1 with α-glucan and β-glucan on Glu156 and Lys157 that plays a role in the interaction with CD63. Therefore, TIMP-1 can be a candidate for a new ligand on colon cancer targeted therapy. Cetuximab and Pleurotus ostreatus Extract (POE) combinations inhibited the survival of HT-29 cells. The α-glucan and β-glucan may partially inhibit TIMP-1 so that the possibility of resistance due to the interaction of TIMP-1 with CD63 can be inhibited and polysaccharide from Pleurotus ostreatus has anticancer activity on HT-29 cells.

Non-real eigenvalues of the harmonic oscillator perturbed by an odd, two-point interaction

In this paper, we consider the perturbations of the Harmonic Oscillator Operator by an odd pair of point interactions: $z (\delta(x - b) - \delta(x + b))$. We study the spectrum by analyzing a convenient formula for the eigenvalue. We conclude that if $z = ir$, $r$ real, as $r \to \infty$, the number of non-real eigenvalues tends to infinity.

Molecular dynamics simulation study of AG10 and tafamidis binding to the Val122Ile transthyretin variant

Molecular dynamics (MD) simulations were used to investigate the binding of four ligands to the Val122Ile mutant of the protein transthyretin. Dissociation, misfolding, and subsequent aggregation of mutated transthyretin proteins are associated with the disease Familial Amyloidal Cardiomyopathy. The ligands investigated were the drug candidate AG10 and its decarboxy and N-methyl derivatives along with the drug tafamidis. These ligands bound to the receptor in two halogen binding pockets (HBP) designated AB and A’B’. Inter-ligand distances, solvent accessible surface areas, root mean squared deviation measurements, and extracted structures showed very little change in the AG10 ligands' conformations or locations within the HBP during the MD simulation. In addition, the AG10 ligands experienced stable, two-point interactions with the protein by forming hydrogen bonds with Ser-117 residues in both the AB and A’B’ binding pockets and Lysine-15 residues found near the surface of the receptor. Distance measurements showed these H-bonds formed simultaneously during the MD simulation. Removal of the AG10 carboxylate functional group to form decarboxy-AG10 disrupted this two-point interaction causing the ligand in the AB pocket to undergo a conformational change during the MD simulation. Likewise, addition of a methyl group to the AG10 hydrazone functional group also disrupted the two-point interaction by decreasing hydrogen bonding interactions with the receptor. Finally, MD simulations showed that the tafamidis ligands experienced fewer hydrogen bonding interactions than AG10 with the protein receptor. The tafamidis ligand in pocket A’B’ was also found to move deeper into the HBP during the MD simulation.

Selective Interaction of Dopamine with the Self-Assembled Fibrillar Network of a Molecular Hydrogel Revealed by STD-NMR.

A molecular hydrogel formed by a derivative of L-valine with pendant isonicotinoyl moieties interacts selectively with protonated dopamine in the presence of related compounds such as 3-methylcatechol, and protonated or neutral phenethylamine. A two-point interaction with the gel fibers is postulated to explain the results. The conclusions are obtained from nuclear magnetic resonance saturation transfer experiments (STD-NMR), illustrating how this technique is perfectly suited to monitor the interaction of substrates with the fibrillar network of a molecular gel.

Density-Functional Theoretical Study on the Role of Lewis and Brønsted Acid Sites on CeO2(110) Surfaces for Nitrile Hydration

Hydration of cyanopyridine on CeO2(110) surfaces was studied using periodic DFT+U calculations. One of two adsorption modes of 2-cyanopyridine occurs with two-point interaction which causes substrate specificity. A catalytic cycle for the hydration of 2-cyanopyridine was proposed. Cooperativity of Lewis and Bronsted acid sites was found to stabilize the intermediates for the hydration.

Acceleration of an Aromatic Claisen Rearrangement via a Designed Spiroligozyme Catalyst that Mimics the Ketosteroid Isomerase Catalytic Dyad

A series of hydrogen-bonding catalysts have been designed for the aromatic Claisen rearrangement of a 1,1-dimethylallyl coumarin. These catalysts were designed as mimics of the two-point hydrogen-bonding interaction present in ketosteroid isomerase that has been proposed to stabilize a developing negative charge on the ether oxygen in the migration of the double bond.1 Two hydrogen bond donating groups, a phenol alcohol and a carboxylic acid, were grafted onto a conformationally restrained spirocyclic scaffold, and together they enhance the rate of the Claisen rearrangement by a factor of 58 over the background reaction. Theoretical calculations correctly predict the most active catalyst and suggest that both preorganization and favorable interactions with the transition state of the reaction are responsible for the observed rate enhancement.

Asymmetric Noncovalent Synthesis of Self-Assembled One-Dimensional Stacks by a Chiral Supramolecular Auxiliary Approach

Stereoselective noncovalent synthesis of one-dimensional helical self-assembled stacks of achiral oligo(p-phenylenevinylene) ureidotriazine (AOPV3) monomers is obtained by a chiral supramolecular auxiliary approach. The racemic mixture of helical stacks of achiral AOPV3 molecules is converted into homochiral helical stacks, as shown by both spectroscopic measurements and molecular modeling simulations. The conversion is promoted by an orthogonal two-point ion-pair interaction with the chiral auxiliary dibenzoyl tartaric acid (D- or L-TA) molecules, which biases the angle population distribution and thereby the stack helicity. The induced preferred helicity is maintained by the OPV stacks even after the removal of the chiral auxiliary by extraction with ethylenediamine (EDA), due to the kinetic stability of the OPV stacks at room temperature. Spectroscopic probing of the helical self-assembly and the racemization process of these π-conjugated OPV chromophores shed further light into the mechanistic pathways of this chiral asymmetric noncovalent synthesis and the kinetic stability of the stacks produced. The racemization of the stacks follows first-order kinetics and no switch in mechanism is observed as a result of a temperature change; therefore, a racemization via disassembly assembly is proposed. Remarkably, the preferred helicity of the stacks of achiral AOPV3 can be retained almost completely after a heating-cooling cycle where the stacks first partially depolymerize and then polymerize again with the still existing stacks being the seeds for self-assembly of achiral AOPV3. Only after a fully dissociated state is obtained at high temperatures, the optical activity of the supramolecular stack self-assembled at room temperature is lost.

Enantio- and Regioselective Epoxidation of Olefinic Double Bonds in Quinolones, Pyridones, and Amides Catalyzed by a Ruthenium Porphyrin Catalyst with a Hydrogen Bonding Site

An array of differently substituted 3-alkenylquinolones was synthesized, and the enantio- and regioselectivity of their Ru-catalyzed epoxidation were studied. A precursor ruthenium(II) complex with a chiral tricyclic γ-lactam skeleton (octahydro-1H-4,7-methanoisoindol-1-one) was available by Sonogashira cross-coupling with a monobromo-substituted ruthenium(II) porphyrin. Enantioselective epoxidation reactions (60-83% yield, 85-98% ee) were achieved with this catalyst, and it was shown that the enantioselectivity depends critically on the presence of a two-point hydrogen bond interaction between the γ-lactam site of the catalyst and the δ-lactam (quinolone) site of the substrate. DFT calculations support the hypothesis that the reaction occurs via a hydrogen-bound transition state, in which the 3-alkenylquinolone adopts an s-trans conformation. The calculations further revealed that this transition state is preferred over a competing s-cis transition state because it exerts less strain in the rigid backbone and because the hydrogen bond interaction is more stable. The catalyst loading required for complete conversion was low (<0.2 mol %), and turnover numbers exceeding 4000 were recorded. It was shown that there is little, if any, inhibition of the catalytic process by other quinolones, which could potentially compete with the binding site. A mechanistic model for the catalytic reaction is presented. In accordance with this model 3-alkenylpyridones reacted with similar enantioselectivities as the respective quinolones. The epoxidation products were unstable, however, and the enantiomeric purity (77-87% ee) of the products could be established only after derivatization. Primary alkenoic acid amides also underwent the epoxidation but gave the respective products in lower enantioselectivities (70% and 45% ee), presumably because the enantioface differentiation is hampered by the increased flexibility of the substrates, which exhibit two or three rotatable single bonds between the binding site and the reactive olefinic double bond.

Phosphopeptide Selective Coordination Complexes as Promising Src Homology 2 Domain Mimetics

Src Homology 2 (SH2) domains are the paradigm of phosphotyrosine (pY) protein recognition modules and mediate numerous cancer-promoting protein-protein complexes. Effective SH2 domain mimicry with pY-binding coordination complexes offers a promising route to new and selective disruptors of pY-mediated protein-protein interactions. We herein report the synthesis and in vitro characterization of a library of coordination complex SH2 domain proteomimetics. Compounds were designed to interact with phosphopeptides via a two-point interaction, principally with pY, and to make secondary interactions with pY+2/3, thereby achieving sequence-selective discrimination. Here, we report that lead mimetics demonstrated high target phosphopeptide affinity (K(a) ∼ 10(7) M(-1)) and selectivity. In addition, biological screening in various tumor cells for anticancer effects showed a high degree of variability in cytotoxicity among receptors, which supported the proposed two-point binding mode. Several receptors potently disrupted cancer cell viability in breast cancer, prostate cancer, and acute myeloid leukemia cell lines.

Synthesis and Photophysical Properties of a Supramolecular Host–Guest Assembly Constructed by Fullerenes and Tryptamine Modified Hypocrellin

The metal coordination polymer of hypocrellin A bearing tryptamine motif (M-DTrpHA) can include fullerene via a two-point interaction, involving π-π stacking and electron donor-acceptor interaction. The 1:1 host-guest system M-DTrpHA/fullerene exhibits a moderate association constant K(a) (6.62 × 10(4) to 6.46 × 10(5) M(-1)). Both of the metal ions in M-DTrpHA and the substituents connected to the fullerene core play important roles in stabilizing the M-DTrpHA/fullerene complex. Transient absorption spectral and NIR absorption spectral results demonstrate that, in the M-DTrpHA/fullerene system, efficient photoinduced electron transfer from the tryptamine group in M-DTrpHA to fullerene may occur, resulting in a long-lived fullerene anion radical. The observed order of quantum yield (Φ(ET)(T)) and rate constants (K(ET)(T)) for electron transfer via (3)C(60)(*) is Y(3+)-DTrpHA > La(3+)-DTrpHA > DTrpHA, consistent with their binding ability to C(60). The nanostructure of M-DTrpHA is rearranged to form an interpenetrating network after interaction with fullerene.

Flavour-coherent propagators and Feynman rules: covariant cQPA formulation

We present a simplified and generalized derivation of the flavour-coherent propagators and Feynman rules for the fermionic kinetic theory based on coherent quasiparticle approximation (cQPA) [1–7]. The new formulation immediately reveals the composite nature of the cQPA Wightman function as a product of two spectral functions and an effective two-point interaction vertex, which contains all quantum statistical and coherence information. We extend our previous work to the case of nonzero dispersive self-energy, which leads to a broader range of applications. By this scheme, we derive flavoured kinetic equations for local 2-point functions $$ S_{\text{k}}^{{ <, > }} $$ (t, t), which are reminiscent of the equations of motion for the density matrix. We emphasize that in our approach all the interaction terms are derived from first principles of nonequilibrium quantum field theory.

Self-assembling effects and mechanisms of interchromophore interactions in porphyrin pentads

The directional self-assembly of nanosized, structurally organized pentads that include five tetrapyrrole macrocycles and are based on the two-point coordination interaction of two covalently bound dimers of Zn porphyrins (homo-and heterodimers) with molecules of either the free base or the Cu complex of tetrametapyridyl-substituted porphyrin extra ligand is implemented in methylcyclohexane at 295 K. Using the method of the density functional theory (DFT) in the B3LYP/6-31g(d) approximation, the geometry of the pentad is fully optimized and the main factors that determine its redox properties are determined. The energies of the lowest excited states of the pentad are calculated by the ZINDO/S method, and it is shown that the occurrence of identical molecules in the system facilitates the formation of excitonic states with different contributions from the charge-transfer component. The directional energy transfer and the photoinduced electron transfer, which leads to the formation of a low-lying charge-transfer state (CT state), are studied and the rate constants of these two processes are determined (kET ∼ 1011 s−1 and kPET ≈ (1.8−6.0) × 109 s−1, respectively). The strong effect of the temperature of the solvent on the efficiency of relaxation processes in pentad complexes under study is revealed and studied. Roles played by the low-lying CT state and d-π exchange effects (the Cu-contained pentad) in fluorescence quenching of pentad complexes are determined.

Folding a Polymer via Two-Point Interaction with an External Folding Agent: Use of H-Bonding and Charge-Transfer Interactions

A polymer containing electron-rich aromatic donors (1,5-dialkoxynaphthalene (DAN)) was coerced into a folded state by an external folding agent that contained an electron-deficient aromatic acceptor (pyromellitic diimide (PDI)) unit. The donor-containing polymer was designed to carry a tertiary amine moiety in the linking segment, which served as an H-bonding site for reinforcing the interaction with the acceptor containing folding agent that also bore a carboxylic acid group. The H-bonding interaction of the carboxylic acid and the tertiary amine brings the PDI unit between two adjacent DAN units along the polymer backbone to induce charge-transfer (C-T) interactions, and this in turn causes the polymer chain to form a pleated structure. Evidence for the formation of such a pleated structure was obtained from NMR titration studies and also by monitoring the C-T band in their UV−visible spectra. By varying the length of the segment that links the PDI acceptor to the carboxylic acid group, we showed that the most effective folding agent was the one that had a single carbon spacer, as evident from the highest value of the association constant. Control experiments with propionic acid clearly demonstrated the importance of the additional C-T interactions for generating the folded structures. Further, solution viscosity measurements in the presence of varying amounts of the folding agent revealed a gradual stiffening of the chain in the case of the PDI carrying carboxylic acid, whereas no such affect was seen in the case of simple propionic acid. These observations were supported by DFT calculations of the interactions of a dimeric model of the polymer with the various folding agents; here too the stability of the complex was seen to be highest in the case of the single carbon spacer.

Two-Step Folding of Donor−Acceptor Foldamers

In a series of polymers containing alternately placed electron-rich dialkoxynaphthalene (DAN) donors and electron-deficient pyromellitic diimide (PDI) acceptors linked by hexa(oxyethylene) (OE-6) segments, the ability to form a folded D-A stack was intentionally disrupted by random inclusion of varying amounts of a comonomer that is devoid of DAN donor units. NMR spectroscopic studies of folding in these copolymers, induced by NH4SCN that coordinates with the OE-6 segments and facilitates the charge-transfer (C-T) induced D-A stacking, clearly reveals the presence of PDI units that are isolated and those that are located at the ends of (D-A)n stacks. Similar conclusions regarding the presence of stacked and unstacked regions along the polymer chain were also inferred from UV−vis spectroscopic studies that probe the evolution of charge-transfer band. One fascinating aspect of these copolymers was their ability to undergo a two-step folding: first, short (D-A)n stacks are formed by the interaction of the NH4+ ion with some specific regions of the polymer chain, and subsequently these stacks are further stacked via a two-point interaction with a suitably designed external folding agent that carries a DAN unit and an ammonium group. In the second step, the interaction first occurs by the coordination of the ammonium group of the folding agent with the OE-6 segment, which in turn facilitates the C-T interaction of the DAN unit with the adjacent uncomplexed PDI units along the polymer chain, leading to an increase in the stacking. Variations of several spectral features, during both UV−vis and NMR spectroscopic titrations, clearly reveal this novel two-step folding process.

Using Self-Assembled Monolayers to Model Cell Adhesion to the 9th and 10th Type III Domains of Fibronectin

Most mammalian cells must adhere to the extracellular matrix (ECM) to maintain proper growth and development. Fibronectin is a predominant ECM protein that engages integrin cell receptors through its Arg-Gly-Asp (RGD) and Pro-His-Ser-Arg-Asn (PHSRN) peptide binding sites. To study the roles these motifs play in cell adhesion, proteins derived from the 9th (containing PHSRN) and 10th (containing RGD) type III fibronectin domains were engineered to be in frame with cutinase, a serine esterase that forms a site-specific, covalent adduct with phosphonate ligands. Self-assembled monolayers (SAMs) that present phosphonate ligands against an inert background of tri(ethylene glycol) groups were used as model substrates to immobilize the cutinase-fibronectin fusion proteins. Baby hamster kidney cells attached efficiently to all protein surfaces, but only spread efficiently on protein monolayers containing the RGD peptide. Cells on RGD-containing protein surfaces also displayed defined focal adhesions and organized cytoskeletal structures compared to cells on PHSRN-presenting surfaces. Cell attachment and spreading were shown to be unaffected by the presence of PHSRN when compared to RGD alone on SAMs presenting higher densities of protein, but PHSRN supported an increased efficiency in cell attachment when presented at low protein densities with RGD. Treatment of suspended cells with soluble RGD or PHSRN peptides revealed that both peptides were able to inhibit the attachment of FN10 surfaces. These results support a model wherein PHSRN and RGD bind competitively to integrins―rather than a two-point synergistic interaction―and the presence of PHSRN serves to increase the density of ligand on the substrate and therefore enhance the sticking probability of cells during attachment.

Twisted, Two-Faced Porphyrins as Hosts for Bispyridyl Fullerenes: Construction and Photophysical Properties

A new class of multichromophoric host compounds capable of binding guest species through two-point coordinative interaction is reported. The hosts contain appended zinc porphyrin (ZnP) moieties connected covalently by acetylene linkages to a central oxoporphyrinogen (OxP) unit through its central macrocyclic nitrogen atoms. Orientation of the ZnP groups was controlled to some extent by variation of the substitution pattern at the OxP N-substituent. Up to four porphyrin appendages are accommodated, and two cofacial bis-porphyrin interaction sites can be created in orthogonal geometry within the same molecule. The multiporphyrin hosts, termed “twisted, two-faced porphyrins”, abbreviated as OxP−(MPx)n where M = 2H or Zn, n = 2 or 4, and x = meta (m) or para (p), and their complexes with a bis-4-pyridyl-substituted fullerene derivative were investigated using spectroscopic, electrochemical, and photochemical methods. Porphyrin fluorescence emission of the OxP−(ZnPx)n compounds is quenched substantially compar...